Transforming growth factor-β (TGF-β)-resistant B cells from chronic lymphocytic leukemia patients contain recurrent mutations in the signal sequence of the type I TGF-β receptor
| Autor: | Kanti R. Rai, Marshall E. Kadin, Petra Knaus, Edi Levi, Waither M Pfeifer, Diana Rotzer, William P. Schiemann |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Signal peptide
Cancer Research Chronic lymphocytic leukemia Molecular Sequence Data Mutant Protein Sorting Signals Biology medicine.disease_cause Polymerase Chain Reaction Sensitivity and Specificity Transforming Growth Factor beta immune system diseases hemic and lymphatic diseases medicine Humans Genetic Predisposition to Disease Receptor Gene Cells Cultured B-Lymphocytes Mutation Base Sequence medicine.disease Leukemia Lymphocytic Chronic B-Cell Molecular biology Leukemia Oncology Drug Resistance Neoplasm Receptors Transforming Growth Factor beta Transforming growth factor |
| Zdroj: | Cancer Detection and Prevention. 28:57-64 |
| ISSN: | 0361-090X |
| Popis: | B cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in western societies, and is currently incurable. B cells of some B-CLL patients are resistant to the anti-proliferative effects of transforming growth factor-beta (TGF-beta). Herein, we identified two mutations within the putative signal sequence of TGF-beta type I receptor (TbetaR-I) gene of TGF-beta-resistant B-CLL patients (i.e., a Leu12Gln substitution together with an in-frame single Ala deletion). Although TbetaR-I mutants were expressed to the cell surface and interacted normally with TGF-beta-bound TbetaR-II, their expression significantly reduced gene transcription stimulated by TGF-beta, suggesting a causal relationship in the development of TGF-beta-resistant B-CLL. Screening of additional B-CLL patients solely for the presence of TbetaR-I signal sequence mutations showed that these mutations correlated with and predicted for B-CLL patient insensitivity to TGF-beta. Our results demonstrate that TGF-beta-resistant B-CLL is linked to signal sequence mutations within the TbetaR-I gene, and may eventually be employed as a prognostic indicator in B-CLL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect